Historically, osteoporosis was defined as a disease in which there is "too little bone, but there is, is normal."Challenges to the assumption that osteoporotic bone mineral is "normal" have yielded inconsistent results. As a result of poor research design and sample selection problems, as well as a scarcity of well defined animal models, published data both contrad and confirm the historical definition. Because of these difficulties, it has been hard both to access the contribution of mineral quality to mechanical properties, and to select therapies which optimize bone properties. By coupling a light microscope to an infrared spectrometer, spectral data can now be obtained at known sites in a histologic section of mineralized tissue without loss of orientation, permitting quantitative assessment of mineral quality (crystallite size and perfection; mineral to matrix ratio) at well-defined morphologic locations. In this project, Fourier transform infrared (FT-IR) microscopy will be used to map mineral properties (crystallite size, mineral:matrix ratio, carbonate content) at 20/micro resolution in trabecular and compact bone in biopsies from osteoporotic humans and from animal's with osteoporosis. The FT-IR data obtained from histologic sections will be correlated with density measured by back-scatter electron imaging (BSE) and histomorphometric parameters, and confirmed by x-ray diffraction and chemical analyses of bulk specimens. Five hypotheses will be tested: 1) Changes in mineral quality with bone age (distance from the center of a single osteon) can be accurately and precisely determined--by mapping changes in mineral quality as a function of distance within an osteon for different osteons from the same biopsy specimen, and comparing these with BSE images quantitated by densitometry. 2) Mineral quality in trabecular and cortical bone correlated with specific histomorphometric parameters rather than being a function of biopsy site, per se--by mapping the spatial variation at different sites in multiple biopsies from a single individual (necropsy specimens). 3) Mineral quality in osteoporosis is related to cellular activity--by comparing mineral quality with histomorphometric measures of cellular activity in biopsies from patients with 3 types of osteoporosis (high turnover, low turnover, and disuse). 4) Animal models may accurately reflect human osteoporoses of these 3 types--by comparing FT--IR maps of bones and biopsies from animal models with each of these 3 conditions to appropriate controls. 5) Therapies for osteoporosis produce changes in mineral quality which vary with therapy and type of osteoporosis--by determining the effects of selected therapies on spatial and temporal changes in mineral quality in humans and in animal models.